Pulmonary hypertensionSitaxsentan Treatment for Patients With Pulmonary Arterial Hypertension Discontinuing Bosentan
Section snippets
Patient Selection
Patients between 12 and 75 years of age with PAH, who had discontinued bosentan because of either safety concerns or inadequate efficacy, as determined by the investigator (worsening hemodynamics, lack of clinically significant response, clinically significant worsening in 6MWD and/or worsening in WHO functional class), were eligible if they met the following criteria: (1) PAH that was idiopathic (IPAH), or associated with connective-tissue disease (CTD) or congenital heart defect (CHD), either
Baseline Characteristics
Forty-eight patients were enrolled: 13 (27%) discontinued bosentan because of safety issues and 35 (73%) because of inadequate efficacy. Table 1 shows baseline characteristics of patients by sitaxsentan dose and reason for discontinuing bosentan. Twenty-two patients (46%) had IPAH; 15 (31%) had PAH associated with CTD; and 11 (23%) PAH associated with CHD. The mean baseline 6MWD was 338 meters. Most patients were WHO Class III at baseline (n = 28; 58%). Of note, those patients with WHO Class
Discussion
Over the past several decades, research has prompted new insights into PAH evidence-based treatment; however, the disease remains progressive and fatal in many patients. In 2001, bosentan was the first oral drug approved for treatment of PAH. Bosentan represents a significant clinical advance in the treatment of PAH; however, not all patients tolerate bosentan or adequately improve.16, 33 The question is whether bosentan discontinuation for inadequate efficacy or safety issues implies an
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Cited by (64)
Hemodynamic Stability After Transitioning Between Endothelin Receptor Antagonists in Patients With Pulmonary Arterial Hypertension
2013, Canadian Journal of CardiologyDefining the affinity and receptor sub-type selectivity of four classes of endothelin antagonists in clinically relevant human cardiovascular tissues
2012, Life SciencesCitation Excerpt :Clinical trial data were disappointing in this condition, however subsequently two antagonists, the non-selective compound bosentan (Tracleer) (Rubin et al., 2002) and the ETA antagonist ambrisentan (Letairis, Volibris) (Vatter and Seifert, 2006) have been introduced for treatment of pulmonary arterial hypertension (PAH). The more ETA selective antagonist sitaxentan (Thelin) (Benza et al., 2007; Galie et al., 2009) was recently withdrawn voluntarily from the market. Although endothelin receptor antagonists have become established as having therapeutic benefit in PAH (Liu et al., 2009; McLaughlin et al., 2009), the relative merits of mixed ETA/ETB or selective ETA antagonism continue to be debated (Davie et al., 2009; Dupuis and Hoeper, 2008; Vachiery and Davenport, 2009).
Endothelin receptor antagonists-their role in pulmonary medicine
2011, Revue des Maladies RespiratoiresTadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension
2011, Journal of Heart and Lung TransplantationThe systemic sclerodermas and related disorders
2011, Textbook of Pediatric RheumatologyCombination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan
2010, International Journal of CardiologyCitation Excerpt :Whether selectivity of receptor blockade matters in regard to efficacy is debatable. Sitaxentan has been found to be useful after failure of treatment with bosentan as well [1,2]. Sildenafil has been licensed for use in the treatment of iPAH and has been shown to improve haemodynamic and functional capacity.
Supported by Encysive Pharmaceuticals, Houston, Texas.